Breaking news in heart failure: ESC Guidelines 2016, non-steroidal mineralocorticoid receptor antagonist, and alternate site CRT pacing

Download the Issue @ a Glance podcast Subscribe to the EHJ Podcast Heart failure is a growing problem in cardiovascular medicine as an end stage of a variety of cardiac diseases including infarction,1 hypertension,2 diabetes,3,4 myocardial and congenital heart disease,5 as well as in the peripartum period.6 Indeed, as we are able to treat, but not to cure, many patients end up with heart failure with preserved or reduced ejection fraction. We will soon be celebrating the 30th anniversary of clinical trials that for the first time convincingly showed that the miserable outcome of patients with heart failure can be improved.7 Recently, important progress has been made in drug treatment8 as well as use of devices in heart failure.9 Thus, the new 2016 ‘ESC Guidelines on Acute and Chronic Heart Failure’ are published at a very timely moment. Authored by the Authors and Task Force Committee, the aim of all the ESC Guidelines is to help health professionals to make appropriate clinical decisions in their everyday practice based on the best available evidence.10 Over the last three decades, heart failure management has experienced and celebrated numerous highs, which have definitely outnumbered several lows, all of which have allowed us to unravel the pathophysiology of this clinical syndrome, but more importantly have led to better care of patients.11 In the year 2016, no one will dispute that, by applying all evidence-based discoveries, heart failure is becoming a preventable and treatable disease, and this document aims to provide practical, evidence-based guidelines for the diagnosis and treatment of heart failure. The most important novel aspects of the 2016 guidelines are summarized in the Ten Commandements in the CardioPulse section of this issue. The Guidelines are accompanied by a Joint Editorial published by the American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) on the use of the so-called ARNIs, i.e. novel combination drugs inhibiting both the angiotensin II type1 receptor and the breakdown of natriuretic peptides.12 The diagnosis of heart failure is stil mainly based on clinical findings, most importantly pulmonary congestion. Although the stethoscope has been used since 1816 when René Laennec introduced it into clinical practice,13 it is known to be less than perfect. Indeed, extravascular lung water is a key variable in heart failure management and outcome, but its objective assessment remains difficult. In a Clinical Review entitled ‘Ultrasound of extravascular lung water: a new standard for pulmonary congestion’, Eugenio Picano from the National Research Council in Pisa, Italy14 describes the use of ultrasound in this context. Lung imaging has been traditionally considered off-limits for ultrasound techniques due to the acoustic barrier of the high impedance air wall. In pulmonary congestion, however, the presence of both air and water creates a peculiar echo fingerprint. Lung ultrasound shows B-lines, comet-like signals arising from a hyperechoic pleural line with a to-and-fro movement synchronized with respiration. Increasing extravascular lung water accumulation changes the normal, no-echo signal with lung tissue appearing black in the absence of extravascular water into a black and white pattern with interstitial subpleural oedema with multiple B-lines or a white lung pattern in the presence of alveolar pulmonary oedema with coalescing B-lines. The number and spatial extent of B-lines on the anterolateral chest allow a semi-quantitative estimation of extravascular lung water from absent, <5, to severe pulmonary oedema with >30 B-lines. Wet B-lines are made by water and decreased by diuretics, which cannot modify dry B-lines made of connective tissue. Of note, B-lines can be evaluated anywhere including under extreme environmental conditions with pocket-size instruments to detect high-altitude pulmonary oedema, at any time during dialysis to titrate intervention, by anyone such as a novice sonographer after 1 h training on anybody, since the chest acoustic window usually remains patent when echocardiography is not feasible. Cardiologists can achieve much diagnostic gain with little investment of technology, training, and time. B-lines represent ‘the shape of lung water’. They allow non-invasive detection, in real time, of even subclinical forms of pulmonary oedema with a low cost, radiation-free approach. In summary, therefore, lung ultrasound may be a most useful novel tool to examine patients with acute heart failure and to monitor those with the chronic form of the disease. Proportion of patients with a decrease of >30% in plasma N-terminal pro-B-type natriuretic peptide concentration from baseline at Day 90 (full-analysis set). Patients who died prior to Day 90 or who experienced permanent (≥5 consecutive days) withdrawal of study drug after a cardiovascular hospitalization or emergency presentation for worsening chronic heart failure were counted as nonresponders for the primary efficacy analysis. (From Filippatos G, Anker SD, Bohm M, Gheorghiade M, Kober L, Krum H, Maggioni AP, Ponikowski P, Voors AA, Zannad F, Kim SY, Nowack C, Palombo G, Kolkhof P, Kimmeskamp-Kirschbaum N, Pieper A, Pitt B. A randomized controlled study of finerenone vs eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. See pages 2105–2114). Fluoroscopy and echo images illustrating the implant procedure. (From Morgan JM, Biffi M, Gellér L, Leclercq C, Ruffa F, Tung S, Defaye P, Yang Z, Gerritse B, van Ginneken M, Yee R, Jais P, on behalf of the ALSYNC Investigators. ALternate Site Cardiac ResYNChronization (ALSYNC): a prospective and multicentre study of left ventricular endocardial pacing for cardiac resynchronization therapy. See pages 2118–2127). Activation of neurohumoral hormones, among them aldosterone, importantly contributes to the dismal outcome of heart failiure. Indeed, inhibition of the mineralocorticoid receptor with steroid-like antagonsist such as spirioloactone and eplerenone markedly reduced events in such patients.15 Non-steroidal mineralocorticoid receptor antagonists may have a better safety profile. In a FAST TRACK entitled ‘A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes and/or chronic kidney disease’ Gerasimos Filippatos and colleagues from the Attikon University Hospital in Athens, Greece evaluated different oral dosages of the non-steroidal mineralocorticoid receptor antagonist finerenone over 3 months in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes.16 ARTS-HF was a double-blind, phase 2B multicentre study that randomized 1066 patients. Patients received either once-daily finerenone at 2.5, 5, 7.5, 10, or 15 mg and then were up-titrated to 5, 10, 15, 20, or 20 mg, respectively, on day 30 or eplerenone 25 mg every other day which was increased to 25 mg once daily on day 30, and to 50 mg once daily on day 60 over 3 months. The primary endpoint was the percentage of individuals with a decrease of >30% in plasma N-terminal pro brain natriuretic peptide (NT-proBNP) at 3 months. NT-proBNP decreased in 37% of patients in the eplerenone group and in 31, 33, 37, 39, and 34% in the 2.5→5 mg, 5→10 mg, 7.5→15 mg, 10→20 mg, and 15→20 mg finerenone groups, respectively. Except for the 2.5→5 mg finerenone group, the composite clinical endpoint occurred less frequently in finerenone-treated patients compared with eplerenone, with the greatest risk reduction observed in the 10→20 mg group with a hazard ratio of 0.56 (Figure 1). A potassium level increase to ≥5.6 mmol/L occurred in only 4.3% of patients, with a balanced distribution among all treatment groups. The authors conclude that finerenone was well tolerated and induced a similar decrease in NT-proBNP levels to eplerenone. The finding of reduced clinical events in the finerenone 10→20 mg group should be further explored in a large outcomes trial. The findings are discussed in an Editorial by Matthias Naegele from the University Hospital Zurich in Switzerland.17 In patients with heart failure and left bundle branch block and widened QRS complex on the ECG, biventricular pacing provides substantial benefit, particularly when effective pacing is provided.18 However, placement of the left ventricular electrode can be challenging in some cases. In their study ‘ALternate Site Cardiac ResYNChronization (ALSYNC): a prospective and multicentre study of left ventricular endocardial pacing for cardiac resynchronization therapy’, John Mark Morgan from Southampton University Hospitals in the UK and investigators evaluated in the ALSYNC Study the feasibility and safety of left ventricular endocardial pacing using a market-released pacing lead implanted via a single pectoral access by a novel atrial–transseptal lead delivery system (Figure 2).19 ALSYNC was a prospective clinical investigation with a minimum of 12 months follow-up in 18 centres of cardiac resynchronization therapy-indicated patients, who had failed or were unsuitable for conventional cardiac resynchronization therapy. The ALSYNC system comprises the investigational lead delivery system and left ventricular endocardial pacing lead. The study enrolled 138 patients, and the left ventricular endocardial pacing lead implant success rate was 89%. Freedom from complications meeting the definition of the primary endpoint reached 82% at 6 months. Fourteen transient ischaemic attacks, 5 non-disabling strokes, and 23 deaths occurred, with none of the deaths being a primary endpoint complication. At 6 months, the New York Heart Association class improved in 59% of patients, and 55% had a left ventricular end-systolic volume reduction of ≥15%. Those patients enrolled after cardiac resynchronization therapy non-response showed similar improvement with left ventricular endocardial pacing. The authors therefore conclude that the ALSYNC study demonstrates clinical feasibility, and provides an early indication of possible benefit and risk of left ventricular endocardial pacing. The editors hope that the readers of this issue of the European Heart Journal will find it of interest.